{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T13:19:36Z","timestamp":1785590376556,"version":"3.56.0"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Brain Research"],"published-print":{"date-parts":[[2014,3]]},"DOI":"10.1016\/j.brainres.2014.01.051","type":"journal-article","created":{"date-parts":[[2014,2,5]],"date-time":"2014-02-05T13:42:08Z","timestamp":1391607728000},"page":"1-9","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":46,"special_numbering":"C","title":["Neuroprotective and anti-apoptotic effects of valproic acid on adult rat cerebral cortex through ERK and Akt signaling pathway at acute phase of traumatic brain injury"],"prefix":"10.1016","volume":"1555","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7990-0110","authenticated-orcid":false,"given":"Chi","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwei","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shushan","family":"Sang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianrui","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.brainres.2014.01.051_bib1","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1038\/sj.cdd.4401097","article-title":"The proapoptotic BH3-only protein BAD transduces cell death signals independently of its interaction with Bcl-2","volume":"9","author":"Adachi","year":"2002","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.brainres.2014.01.051_bib2","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1111\/j.1460-9568.2007.05720.x","article-title":"Hypothermia treatment potentiates ERK1\/2 activation after traumatic brain injury","volume":"26","author":"Atkins","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"10.1016\/j.brainres.2014.01.051_bib3","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1111\/j.1471-4159.2006.04353.x","article-title":"Neuronal NOS-mediated nitration and inactivation of manganese superoxide dismutase in brain after experimental and human brain injury","volume":"101","author":"Bayir","year":"2007","journal-title":"J. Neurochem."},{"key":"10.1016\/j.brainres.2014.01.051_bib4","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.ejcb.2006.04.013","article-title":"The neuroprotective agent, valproic acid, regulates the mitogen-activated protein kinase pathway through modulation of protein kinase A signalling in dictyostelium discoideum","volume":"85","author":"Boeckeler","year":"2006","journal-title":"Eur. J. Cell Biol."},{"key":"10.1016\/j.brainres.2014.01.051_bib5","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1080\/j.1440-1614.2006.01815.x","article-title":"Anticonvulsants in bipolar disorder","volume":"40","author":"Bowden","year":"2006","journal-title":"Aust. N. Z. J. Psychiatry"},{"key":"10.1016\/j.brainres.2014.01.051_bib6","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.neuropharm.2006.05.021","article-title":"Treatment with valproate after status epilepticus: effect on neuronal damage, epileptogenesis, and behavioral alterations in rats","volume":"51","author":"Brandt","year":"2006","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.brainres.2014.01.051_bib7","doi-asserted-by":"crossref","first-page":"630","DOI":"10.3892\/ijmm.2011.870","article-title":"The selective mGluR5 agonist CHPG protects against traumatic brain injury in vitro and in vivo via ERK and Akt pathway","volume":"29","author":"Chen","year":"2012","journal-title":"Int. J. Mol. Med."},{"key":"10.1016\/j.brainres.2014.01.051_bib8","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1089\/neu.2004.21.1168","article-title":"Oxygen free radical-dependent activation of extracellular signal-regulated kinase mediates apoptosis-like cell death after traumatic brain injury","volume":"21","author":"Clausen","year":"2004","journal-title":"J. Neurotrauma."},{"key":"10.1016\/j.brainres.2014.01.051_bib9","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S0962-8924(97)01105-7","article-title":"The search for physiological substrates of MAP and SAP kinases in mammalian cells","volume":"7","author":"Cohen","year":"1997","journal-title":"Trends Cell. Biol."},{"key":"10.1016\/j.brainres.2014.01.051_bib10","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/S0306-4522(02)00277-4","article-title":"The role of extracellular signal-regulated kinase in cognitive and motor deficits following experimental traumatic brain injury","volume":"114","author":"Dash","year":"2002","journal-title":"Neuroscience"},{"key":"10.1016\/j.brainres.2014.01.051_bib11","doi-asserted-by":"crossref","first-page":"e11383","DOI":"10.1371\/journal.pone.0011383","article-title":"Valproate administered after traumatic brain injury provides neuroprotection and improves cognitive function in rats","volume":"5","author":"Dash","year":"2010","journal-title":"PLoS One"},{"key":"10.1016\/j.brainres.2014.01.051_bib12","doi-asserted-by":"crossref","first-page":"e24648","DOI":"10.1371\/journal.pone.0024648","article-title":"Involvement of the glycogen synthase kinase-3 signaling pathway in TBI pathology and neurocognitive outcome","volume":"6","author":"Dash","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.brainres.2014.01.051_bib13","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0092-8674(00)80405-5","article-title":"Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery","volume":"91","author":"Datta","year":"1997","journal-title":"Cell"},{"key":"10.1016\/j.brainres.2014.01.051_bib14","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/S0028-3908(02)00215-0","article-title":"Regulation of Akt and glycogen synthase kinase-3 beta phosphorylation by sodium valproate and lithium","volume":"43","author":"De Sarno","year":"2002","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.brainres.2014.01.051_bib15","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/0-387-30128-3_3","article-title":"DSD-1-Proteoglycan\/Phosphacan and receptor protein tyrosine phosphatase-beta isoforms during development and regeneration of neural tissues","volume":"557","author":"Faissner","year":"2006","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.brainres.2014.01.051_bib16","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0955-0674(99)80028-3","article-title":"Organization and regulation of mitogen-activated protein kinase signaling pathways","volume":"11","author":"Garrington","year":"1999","journal-title":"Curr. Opin. Cell Biol."},{"key":"10.1016\/j.brainres.2014.01.051_bib17","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1083\/jcb.119.3.493","article-title":"Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation","volume":"119","author":"Gavrieli","year":"1992","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.brainres.2014.01.051_bib18","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1161\/01.STR.16.1.101","article-title":"Ischemic brain edema following occlusion of the middle cerebral artery in the rat. I: the time courses of the brain water, sodium and potassium contents and blood\u2013brain barrier permeability to 125I-albumin","volume":"16","author":"Gotoh","year":"1985","journal-title":"Stroke"},{"key":"10.1016\/j.brainres.2014.01.051_bib19","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1471-4159.2004.02695.x","article-title":"Plasma membrane oestrogen receptor mediates neuroprotection against beta-amyloid toxicity through activation of Raf-1\/MEK\/ERK cascade in septal-derived cholinergic SN56 cells","volume":"91","author":"Guerra","year":"2004","journal-title":"J. Neurochem."},{"key":"10.1016\/j.brainres.2014.01.051_bib20","doi-asserted-by":"crossref","first-page":"6181","DOI":"10.1523\/JNEUROSCI.4491-12.2013","article-title":"An activated protein C analog stimulates neuronal production by human neural progenitor cells via a PAR1-PAR3-S1PR1-Akt pathway","volume":"33","author":"Guo","year":"2013","journal-title":"J. Neurosci."},{"key":"10.1016\/j.brainres.2014.01.051_bib21","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s11940-012-0178-5","article-title":"Treatment of post-traumatic epilepsy","volume":"14","author":"Hung","year":"2012","journal-title":"Curr. Treat. Options Neurol."},{"key":"10.1016\/j.brainres.2014.01.051_bib22","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/S0014-5793(03)00350-8","article-title":"Valproic acid, a mood stabilizer and anticonvulsant, protects rat cerebral cortical neurons from spontaneous cell death: a role of histone deacetylase inhibition","volume":"542","author":"Jeong","year":"2003","journal-title":"FEBS Lett."},{"key":"10.1016\/j.brainres.2014.01.051_bib23","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0197-0186(00)00013-9","article-title":"Mechanisms of action of valproate: a commentatory","volume":"37","author":"Johannessen","year":"2000","journal-title":"Neurochem. Int."},{"key":"10.1016\/j.brainres.2014.01.051_bib24","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s11064-006-9251-3","article-title":"Genetic influences on outcome following traumatic brain injury","volume":"32","author":"Jordan","year":"2007","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.brainres.2014.01.051_bib25","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/sj.tpj.6500269","article-title":"Valproic acid inhibits histone deacetylase activity and suppresses excitotoxicity-induced GAPDH nuclear accumulation and apoptotic death in neurons","volume":"4","author":"Kanai","year":"2004","journal-title":"Pharmacogenomics J."},{"key":"10.1016\/j.brainres.2014.01.051_bib26","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1742-2094-6-32","article-title":"Administration of S-nitrosoglutathione after traumatic brain injury protects the neurovascular unit and reduces secondary injury in a rat model of controlled cortical impact","volume":"6","author":"Khan","year":"2009","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.brainres.2014.01.051_bib27","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1046\/j.0953-816x.2000.01409.x","article-title":"Neuroprotection by estrogen via extracellular signal-regulated kinase against quinolinic acid-induced cell death in the rat hippocampus","volume":"13","author":"Kuroki","year":"2001","journal-title":"Eur. J. Neurosci."},{"key":"10.1016\/j.brainres.2014.01.051_bib28","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.surg.2008.03.037","article-title":"Cell protective mechanism of valproic acid in lethal hemorrhagic shock","volume":"144","author":"Li","year":"2008","journal-title":"Surgery"},{"key":"10.1016\/j.brainres.2014.01.051_bib29","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1089\/neu.2010.1518","article-title":"Early post-traumatic seizures in moderate to severe pediatric traumatic brain injury: rates, risk factors, and clinical features","volume":"28","author":"Liesemer","year":"2011","journal-title":"J. Neurotrauma"},{"key":"10.1016\/j.brainres.2014.01.051_bib30","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.neulet.2005.05.057","article-title":"Extracellular signal-regulated kinase-mediated IL-1-induced cortical neuron damage during traumatic brain injury","volume":"386","author":"Lu","year":"2005","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.brainres.2014.01.051_bib31","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.brainresbull.2011.07.007","article-title":"VEGF protects rat cortical neurons from mechanical trauma injury induced apoptosis via the MEK\/ERK pathway","volume":"86","author":"Ma","year":"2011","journal-title":"Brain Res. Bull."},{"key":"10.1016\/j.brainres.2014.01.051_bib32","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.neuropharm.2009.03.006","article-title":"Cocaine-induced hyperactivity and sensitization are dependent on GSK3","volume":"56","author":"Miller","year":"2009","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.brainres.2014.01.051_bib33","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1586\/14737175.8.12.1817","article-title":"Treatment of status epilepticus","volume":"8","author":"Miller","year":"2008","journal-title":"Expert Rev. Neurother."},{"key":"10.1016\/j.brainres.2014.01.051_bib34","article-title":"Effect of valproic acid through regulation of NMDA receptor-ERK signaling in sleep deprivation rats","author":"Park","year":"2011","journal-title":"J. Mol. Neurosci."},{"key":"10.1016\/j.brainres.2014.01.051_bib35","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0304-3940(02)01193-X","article-title":"Neuroprotective effects of anticonvulsants in rat hippocampal slice cultures exposed to oxygen\/glucose deprivation","volume":"335","author":"Rekling","year":"2003","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.brainres.2014.01.051_bib36","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1111\/j.1471-4159.2004.02406.x","article-title":"Valproic acid reduces brain damage induced by transient focal cerebral ischemia in rats: potential roles of histone deacetylase inhibition and heat shock protein induction","volume":"89","author":"Ren","year":"2004","journal-title":"J. Neurochem."},{"key":"10.1016\/j.brainres.2014.01.051_bib37","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/nrn1430","article-title":"The neurobiology of antiepileptic drugs","volume":"5","author":"Rogawski","year":"2004","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.brainres.2014.01.051_bib38","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1007\/s00018-007-7079-x","article-title":"The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees?","volume":"64","author":"Rosenberg","year":"2007","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.brainres.2014.01.051_bib39","doi-asserted-by":"crossref","first-page":"4266","DOI":"10.1096\/fj.09-134700","article-title":"Histone deacetylase inhibitor ITF2357 is neuroprotective, improves functional recovery, and induces glial apoptosis following experimental traumatic brain injury","volume":"23","author":"Shein","year":"2009","journal-title":"FASEB J."},{"key":"10.1016\/j.brainres.2014.01.051_bib40","doi-asserted-by":"crossref","first-page":"6248","DOI":"10.1523\/JNEUROSCI.19-15-06248.1999","article-title":"Exacerbation of damage and altered NF-kappaB activation in mice lacking tumor necrosis factor receptors after traumatic brain injury","volume":"19","author":"Sullivan","year":"1999","journal-title":"J. Neurosci."},{"key":"10.1016\/j.brainres.2014.01.051_bib41","doi-asserted-by":"crossref","first-page":"593","DOI":"10.3171\/jns.1999.91.4.0593","article-title":"Valproate therapy for prevention of posttraumatic seizures: a randomized trial","volume":"91","author":"Temkin","year":"1999","journal-title":"J. Neurosurg."},{"key":"10.1016\/j.brainres.2014.01.051_bib42","first-page":"347","article-title":"Actions of sodium valproate on the central nervous system","volume":"50","author":"Tunnicliff","year":"1999","journal-title":"J. Physiol. Pharmacol."},{"key":"10.1016\/j.brainres.2014.01.051_bib43","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s13311-012-0157-2","article-title":"Scriptaid, a novel histone deacetylase inhibitor, protects against traumatic brain injury via modulation of PTEN and AKT pathway: scriptaid protects against TBI via AKT","volume":"10","author":"Wang","year":"2013","journal-title":"Neurotherapeutics"},{"key":"10.1016\/j.brainres.2014.01.051_bib44","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1126\/science.270.5240.1326","article-title":"Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis","volume":"270","author":"Xia","year":"1995","journal-title":"Science"},{"key":"10.1016\/j.brainres.2014.01.051_bib45","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.brainres.2008.06.018","article-title":"Neuroprotective effect of humanin on cerebral ischemia\/reperfusion injury is mediated by a PI3K\/Akt pathway","volume":"1227","author":"Xu","year":"2008","journal-title":"Brain Res."}],"updated-by":[{"DOI":"10.1016\/j.brainres.2016.08.036","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000}}],"container-title":["Brain Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S000689931400136X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S000689931400136X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T17:53:34Z","timestamp":1757786014000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S000689931400136X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3]]},"references-count":45,"alternative-id":["S000689931400136X"],"URL":"https:\/\/doi.org\/10.1016\/j.brainres.2014.01.051","relation":{"erratum":[{"id-type":"doi","id":"10.1016\/j.brainres.2016.08.036","asserted-by":"object"}]},"ISSN":["0006-8993"],"issn-type":[{"value":"0006-8993","type":"print"}],"subject":[],"published":{"date-parts":[[2014,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Neuroprotective and anti-apoptotic effects of valproic acid on adult rat cerebral cortex through ERK and Akt signaling pathway at acute phase of traumatic brain injury","name":"articletitle","label":"Article Title"},{"value":"Brain Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.brainres.2014.01.051","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2014 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}